Typical examples of the prior art on the preparation of the compound of formula (I), i.e., famciclovir, include European Patent No. 182,024, and U.S. Pat. Nos. 5,684,153, 5,138,057 and 5,917,041.
European Patent No. 182,024 and U.S. Pat. No. 5,684,153 disclose a method for preparing 9-[4-acetoxy-3-(aectoxymethyl)but-1-yl]-2-aminopurine as shown in the following reaction scheme (1), in which 2-amino-6-chloropurine of the following formula (VIII) is reacted with 2-acetoxymethyl-4-halobut-1-yl-acetate of the following formula (IX) to give 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-amino-6-chloropurine of the following formula (X), which is then reduced into the compound of formula (I) in the presence of palladium as a reduction catalyst:

wherein X is a halogen atom.
However, the above preparation method has a severe problem in that, as shown in the following reaction scheme (2), the reaction between the compound of formula (VI II) and the compound of formula (IX) produces not only the compound of formula (X) but also its isomer, 7-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-amino-6-chloropurine of the following formula (XI), at a ratio of 80%:20%, indicating that selectivity for the compound (X) is low and the purification of the compound (X) becomes very difficult:

wherein X is a halogen atom.
Furthermore, the preparation method shown in reaction scheme (1) has a severe problem in that a palladium catalyst, which is highly explosive, must be used in the preparation of the final desired compound of formula (1) from the compound of formula (X). Thus, this method has low process efficiency which makes its industrial application unsuitable.
Meanwhile, U.S. Pat. No. 5,138,057 discloses a method for preparing 9-[4-acetoxy-3-(aectoxymethyl)but-1-yl]-2-aminopurine of the following formula (I) as shown in the following reaction scheme (3), in which 2-amino-6,8-dichloropurine of the following formula (XII) is reacted with 2-acetoxymethyl-4-halobut-1-yl-acetate of the following formula (IX) to yield 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-amino-6,8-dichloropurine of the following formula (XIII) which is then reduced using palladium as a reduction catalyst under a high-pressure condition:

wherein X is a halogen atom.
In this method, by the reaction between the compound of formula (XII) and the compound of formula (IX), not only the compound of formula (XIII) but also its isomer, 7-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-amino-6,8-dichloropurine are produced at a ratio of 94%:6% indicating a somewhat increase in selectivity. However, this method, as in European Patent No. 182,024 and U.S. Pat. No. 5,684,153, also has a severe problem in that the preparation of the final desired compound of formula (I) from the compound of formula (XIII) must be carried out in the presence of a highly explosive palladium catalyst under a high-pressure condition (above 50 psi). For this reason, the industrial application of this method is still difficult.
Furthermore, U.S. Pat. No. 5,971,041 discloses a method for preparing 9-[4-acetoxy-3-(aectoxymethyl)but-1-yl]-2-aminopurine of the following formula (1) as shown in the following reaction scheme (4), in which (N-(2-amino-4,6-dichloro-5-pyrimidinyl)formamide of the following formula (XV) is reacted with 2-Acetoxymethyl-4-aminobut-1-yl-acetate of the following formula (XVI) to give a compound of the following formula (XVII), which is then converted into 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-amino-6-chloropurine using triethylorthoformate of the following formula (XVIII), which is, in turn, reduced into the compound of formula (I) using palladium as a reduction catalyst:

However, this method has problems in that, as shown in the following reaction GIBSON scheme (5), 2,5-diamino-4,6-dihydroxypyrimidine of the following formula (XIX) and chloromethylene iminium salt of the following formula (XX), which are expensive, must be used to prepare the compound of formula (XV) as a starting material, and the final desired compound of formula (I) is obtained at a very low yield of about 32% through several steps from the compound of formula (XXI). Another problem is that the palladium catalyst, which is highly explosive, must be used, as in the prior methods disclosed in EP No. 182,024 and U.S. Pat. No. 5,684,153. Thus, this method has low process efficiency and a long reaction pathway, which make its industrial application difficult.
